Biomedical subjects

Heidar-Ali Tajmir-Riahi

Publications and source records attributed to Heidar-Ali Tajmir-Riahi.

8 recordsLinked to original sources

PubMed2006

Interaction of antioxidant flavonoids with tRNA: intercalation or external binding and comparison with flavonoid-DNA adducts.

Antioxidants are essential to good health. Flavonoids are powerful antioxidants, and prevent DNA damage. The antioxidative protections are related to their binding modes to a DNA duplex and complexation with free radicals in vivo. Recently we reported the interaction of flavonoids with DNA in vitro (Kanakis et al., J. Biomol. Struct. Dyn. 22, 719-724, 2005), where polyphenol different binding modes were discussed. The aim of this study was to examine the interaction of transfer RNA with quercetin (que), kaempferol (kae), and delphinidin (del) in aqueous solution at physiological conditions and to make a comparison with the corresponding pigment-DNA adducts. Constant tRNA concentration (6.25 mM) and various drug/RNA(phosphate) molar ratios of 1/48 to 1/8 were used. FTIR and UV-visible difference spectroscopic methods have been applied to determine the drug binding mode, the binding constants, and the effects of drug complexation on the stability and conformation of tRNA duplex. Both intercalative and external binding modes were observed. Structural analysis showed que, kae, and a del intercalate tRNA duplex with minor external binding to the major or minor groove and the backbone phosphate group with overall binding constants K (que) = 4.80 x 10(4) M(1), K (kae) = 4.65 x 10(4) M(1), and K (del) = 9.47 x 10(4) M(1). The stability of adduct formation is in the order of del > que > kae. A comparison with flavonoids-DNA adducts showed both intercalation and external bindings with the stability order K (que) = 7.25 x 10(4) M(1), K (kae) = 3.60 x 10(4) M(1), and K (del) = 1.66 x 10(4) M(1). Low flavonoid concentration induces helical stabilization, whereas high pigment content causes helix opening. A partial Bto A-DNA transition occurs at high drug concentration, while tRNA remains in the A-family structure.

Anthocyanins↗

PubMed2006

Transfer RNA binding to human serum albumin: a model for protein-RNA interaction.

Protein-RNA complexation is essential in cell biological functions. Transfer RNAs are bound to aminoacyl-tRNA synthetases for the translation of the genetic code during protein synthesis, while ribonucleoproteins bind RNA in posttranscriptional regulation of gene expression. A recent report showed the interacton of human serum albumin (HSA) with DNA duplex, in which two binding sites with strong and weak association constants were detected. We now examine the interaction of tRNA with human serum albumin (HSA) in aqueous solution at physiological conditions, using a constant RNA concentration of 12.5 mM (phosphate) and various HSA contents of 0.04 to 0.6 mM. Affinity capillary electrophoresis and FTIR spectroscopic methods were used to determine the protein binding mode, the association constant, sequence preference, and the biopolymer secondary structural changes in the HSA-RNA complexes. Spectroscopic evidence showed two types of HSA-RNA complexes with an overall binding constant of K = 1.45 x 10(4) M(-1). The major binding sites were located on the G-C bases and the backbone PO2 group. The protein-RNA interaction stabilizes the HSA secondary structure, and no major alterations of A-RNA structure or protein conformation occurred.

Binding Sites↗

PubMed2005

Interaction of arsenic trioxide As2O3 with DNA and RNA.

Arsenic salts have been used for centuries to treat a variety of medical conditions ranging from infectious disease to cancer. More recently, trivalent arsenic trioxide was found to exhibit high antitumor activity towards hematological malignancies. Even though much is known about antitumor activity and DNA damage by As2O3, there has been no report on the interaction of arsenic trioxide with isolated DNA or RNA. Therefore, it was of interest to examine the interaction of As2O3 with DNA and RNA in aqueous solution at physiological pH. FTIR and UV-visible difference spectroscopic methods were used to characterize the nature of drug-DNA and drug-RNA interactions and to determine the As binding site, the binding constant, the sequence selectivity, the helix stability, and the biopolymer secondary structure in the As2O3-polynucleotide complexes in vitro. The FTIR spectroscopic studies were conducted with As2O3-polynucleotide (phosphate) ratios of 1/40, 1/20, 1/10, and 1/5, with a final DNA (P) or RNA (P) concentration of 6.25 mmol/l. Spectroscopic results showed As2O3 binds to DNA and RNA at G-C, A-T, and A-U bases, and no interaction with the backbone PO2 group. As2O3-DNA and -RNA adducts showed one type of binding with overall binding constant of K(As2O3-DNA) = 1.24 x 10(5) M(-1) and K(As2O3-RNA) = 2.60 x 10(5) M(-1). The As2O3-polynucleotide complexation is associated with a partial biopolymer aggregation and no major alterations of B-DNA or A-RNA structure.

Animals↗

PubMed2004

Structural analysis of DNA interactions with biogenic polyamines and cobalt(III)hexamine studied by Fourier transform infrared and capillary electrophoresis.

Biogenic polyamines, such as putrescine, spermidine, and spermine are small organic polycations involved in numerous diverse biological processes. These compounds play an important role in nucleic acid function due to their binding to DNA and RNA. It has been shown that biogenic polyamines cause DNA condensation and aggregation similar to that of inorganic cobalt(III)hexamine cation, which has the ability to induce DNA conformational changes. However, the nature of the polyamine.DNA binding at the molecular level is not clearly established and is the subject of much controversy. In the present study the effects of spermine, spermidine, putrescine, and cobalt(III)hexamine on the solution structure of calf-thymus DNA were investigated using affinity capillary electrophoresis, Fourier transform infrared, and circular dichroism spectroscopic methods. At low polycation concentrations, putrescine binds preferentially through the minor and major grooves of double strand DNA, whereas spermine, spermidine, and cobalt(III)hexamine bind to the major groove. At high polycation concentrations, putrescine interaction with the bases is weak, whereas strong base binding occurred for spermidine in the major and minor grooves of DNA duplex. However, major groove binding is preferred by spermine and cobalt(III)hexamine cations. Electrostatic attractions between polycation and the backbone phosphate group were also observed. No major alterations of B-DNA were observed for biogenic polyamines, whereas cobalt(III)hexamine induced a partial B --> A transition. DNA condensation was also observed for cobalt(III)hexamine cation, whereas organic polyamines induced duplex stabilization. The binding constants calculated for biogenic polyamines are K(Spm) = 2.3 x 10(5) M(-1), K(Spd) = 1.4 x 10(5) M(-1), and K(Put) = 1.02 x 10(5) M(-1). Two binding constants have been found for cobalt(III)hexamine with K(1) = 1.8 x 10(5) M(-1) and K(2) = 9.2 x 10(4) M(-1). The Hill coefficients indicate a positive cooperativity binding for biogenic polyamines and a negative cooperativity for cobalt(III)hexamine.

Binding Sites↗

PubMed2004

AZT-DNA interaction.

Oxidative DNA damage has been reported in fetal tissues by exposure to 3'-azido-3'-deoxythymidine (AZT). AZT has been used effectively for the treatment of human immunodeficiency virus-1 (HIV-1) and AIDS. It showed in vitro to block the nucleoside-binding site of the viral reverse transcriptase and to inhibit DNA replication by chain termination. It incorporates into both nuclear and mitochondrial DNA and is shown to cause cancer in vivo and in vitro. This study was designed to examine the interaction of AZT with DNA in aqueous solution at physiological condition, using different drug/DNA (phosphate) molar ratios (r) of 1/80 to 1/2 and constant DNA concentration of 12.5 mM (phosphate). Capillary electrophoresis, FTIR, and UV-visible difference spectroscopic methods and molecular modeling were used to determine the drug binding sites, the binding constants and the effects of the AZT complexation on DNA conformation. Structural analysis showed that AZT binds to DNA through G-C and A-T base pairs and the backbone PO(2) groups with two binding constants of K(1) = 2.60 x 10(5) M(-1) and K(2) = 1.20 x 10(5) M(-1). The drug distributions are 50% with G-C, 15% with A-T and 35% with the backbone phosphate group. AZT-DNA interaction is associated with a partial B- to A-DNA conformational transition.

Animals↗

PubMed2004

AZT binds RNA at multiple sites.

Azidothymidine (AZT) is a widely used inhibitor of type I human immunodeficiency virus (HIV) reverse transcriptase that act as a DNA chain terminator. Studies have shown primer unblocking and rescue of DNA synthesis AZT-resistant HIV-1 reverse transcriptase on DNA and RNA templates. Our recent study showed AZT bindings to the G-C, A-T base pairs and the backbone phosphate group of DNA duplex resulting in partial DNA conformational changes. This study was designed to examine the interaction of AZT with RNA in aqueous solution at physiological condition, using different drug/RNA (phosphate) molar ratios of 1/800 to 1/2 and constant RNA concentration of 1.25 or 12.5 mM (phosphate). Capillary electrophoresis, FTIR, and UV-visible difference spectroscopic methods and molecular modeling were used to determine the drug binding sites, binding constants, and the effects of AZT complexation on RNA conformation. Structural analysis showed that AZT binds RNA through G-C and A-U bases with two binding constants of K1=7.3 x 10(5) M(-1) and K2=1.90 x 10(5) M(-1). The drug distributions were 54% with G-C, 36% A-U, and 10% with the backbone phosphate group. RNA remains in A-family structure and drug sugar pucker in the C2'-endo/anti conformation in the AZT-RNA complexes. Molecular modeling studies show hydrogen bondings between RNA and AZT donor groups.

Electrophoresis, Capillary↗

PubMed2004

DNA adducts with chlorophyll and chlorophyllin as antimutagenic agents: synthesis, stability, and structural features.

Porphyrins and their metal derivatives are strong DNA binders with association constants of 10(5) M(-1) to 10(7) M(-1). Some of these compounds have been used for radiation sensitization therapy of cancer and are targeted to interact with cellular DNA. Chlorophyll (CHL) and chlorophyllin (CHLN), a food-grade derivative of chlorophyll, the ubiquitous green plant pigment widely consumed by humans, are potent inhibitors of experimental carcinogenesis. The aim of this report was to examine the interaction of calf-thymus DNA with CHL and CHLN in aqueous solution at physiological pH, with pigment/DNA(phosphate) molar ratios (r) of 1/80 to 1/2. Fourier transform infrared (FTIR) difference spectroscopic method was used to determine the pigment binding mode, binding constant, sequence selectivity, DNA secondary structure and structural variations of the pigment-DNA complexes in aqueous solution.

Animals↗

PubMed2003

Control of energy dissipation and photochemical activity in photosystem I by NADP-dependent reversible conformational changes.

Addition of NADP(+) to thylakoid membranes or isolated photosystem I (PSI) submembrane fractions quenched chlorophyll fluorescence by up to 40% at low or room temperature. This quenching was reversed by NADPH. Similar quenching was also observed with the addition of heparin or thenoyltrifluoroacetone (TTFA), inhibitors that bind ferredoxin:NADP(+) reductase (FNR) and prevent reduction of NADP(+). The NADP(+)-induced quenching coincided with a reversible conformational change of the secondary protein structure in the PSI submembrane fractions where 20% of the alpha-helix conformations were transformed mainly into beta-sheet-like structures. Further, P700 photooxidation was retarded due to this conformational change, and about 25% of the centers could not be photooxidized, these changes being also reversible with addition of NADPH. The above modifications in the presence of NADP(+) also increased photodamage processes under strong illumination, and NADPH protected it. Conformational modification of FNR upon binding of NADP(+) or NADPH is proposed to trigger the macromolecular changes in a larger part of the protein complex of PSI. The conformational changes must increase the intermolecular distances and change the mutual orientation between the various cofactors in the PSI complex. This new control mechanism of energy dissipation and photochemical activity by NADP(+)/NADPH is proposed to increase the turnover rate of PSI under conditions when both linear and cyclic electron transport activities must be supported.

Chlorophyll↗